The initial molecular response predicts the deep molecular response but not treatment-free remission maintenance in a real-world chronic myeloid leukemia cohort

In chronic myeloid leukemia, the identification of early molecular predictors of stable treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) discontinuation is challenging. The predictive values of residual disease (BCR::ABL1 quantification) at months 3 and 6 and more recently, BCR::ABL1 transcript halving time (HT) have been described, but no study compared the predictive value of different early parameters. Using a real-world cohort of 408 patients, we compared the performance of the ELTS score, BCR::ABL1 HT, and residual disease at month 3 and 6 to predict the molecular response, achievement of the TKI discontinuation criteria, and TFR maintenance. The performances of BCR::ABL1 HT and residual disease at month 3 were similar. Residual disease at month 6 displayed the best performance for predicting the optimal response (area under the ROC curve between 0.81 and 0.92; cut-off values: 0.11% for MR4 at month 24 and 0.12% for MR4.5 at month 48). Conversely, no early parameter predicted reaching the TKI discontinuation criteria and TFR maintenance. We obtained similar results when patients were divided in subgroups by first-line treatment (imatinib vs second generation TKI, 2G-TKI). We identified a relationship between ELTS score, earlier milestones and TFR maintenance only in the 2G-TKI group. In conclusion, this first comparative study of early therapeutic response parameters showed that they are excellent indicators of TKI efficacy (BCR::ABL1 transcript reduction) and best responders. Conversely, they did not predict the achievement of the TKI discontinuation criteria and TFR maintenance, suggesting that other parameters are involved in TFR maintenance

Structure, Function, and Evolution of the Thiomonas spp. Genome

Bacteria of the Thiomonas genus are ubiquitous in extreme environments, such as arsenic-rich acid mine drainage (AMD). The genome of one of these strains, Thiomonas sp. 3As, was sequenced, annotated, and examined, revealing specific adaptations allowing this bacterium to survive and grow in its highly toxic environment. In order to explore genomic diversity as well as genetic evolution in Thiomonas spp., a comparative genomic hybridization (CGH) approach was used on eight different strains of the Thiomonas genus, including five strains of the same species. Our results suggest that the Thiomonas genome has evolved through the gain or loss of genomic islands and that this evolution is influenced by the specific environmental conditions in which the strains live

Utilisation et évaluation économique des milieux chromogènes pour le diagnostic des infections urinaires en milieu hospitalier

TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

The newcomers: distantly related bacteria have settled as co-obligate symbionts in aphids

National audienc

A New O-Antigen Gene Cluster Has a Key Role in the Virulence of the Escherichia coli Meningitis Clone O45:K1:H7▿

A new highly pathogenic clone of Escherichia coli meningitis strains harboring the unusual serogroup O45 has recently emerged in France. To gain insight into the pathogenicity of this new clone, we investigated the possible role of antigen O45 in the virulence of strain S88 (O45:K1:H7), representative of this emerging clone. We first showed that the S88 O-antigen gene cluster sequence differs from that of O45 in the reference strain E. coli 96-3285, suggesting that the two O45 polysaccharides, while probably sharing a community of epitopes, represent two different antigens. The unique functional organization of the two O-antigen gene clusters and the low DNA sequence homology of the orthologous genes suggest that the two loci originated from a common ancestor and have since undergone multiple recombination events. Phylogenetic analysis based on the flanking gene gnd sequences indicates that the S88 antigen O45 (O45S88) gene cluster may have been acquired, at least in part, from another member of the Enterobacteriaceae. Mutagenesis of the O45S88 antigen gene cluster was used for functional analysis of the loci and revealed the crucial role of the O polysaccharide in S88 virulence in a neonatal rat meningitis model. We also developed a PCR method to specifically identify the O45S88 antigen gene cluster. Together, our findings suggest that horizontal acquisition of a new O-antigen gene cluster, at least partly from another species, may have been a key event in the emergence and virulence of the E. coli O45:K1:H7 clone in France

Ongoing Symbiont Replacement in the Aphid Cinara strobi

National audienc

The coming and going of mutualistic symbionts: The ins and outs of co-obligate endosymbiont replacement in Cinara aphids

International audienceNutritional-based mutualistic associations between microorganisms and insects with unbalanced diets is pervasive, with several insects having developed obligate associations with either bacterial or fungal symbionts. The last common ancestor of Cinara aphids (Hemiptera: Aphididae) harboured two obligate nutritional endosymbionts: Buchnera (the primary obligate endosymbiont of most aphids) and most probably a Serratia symbiotica. The latter shows a very dynamic pattern of replacement by different bacterial taxa, thus offering a special opportunity to study the turnover of obligate mutualistic associations. We have assembled the endosymbionts' genomes from over 60 species of Cinara. We found that most secondary co-obligate endosymbionts belong to taxa commonly associated to aphids as facultative endosymbionts, hinting at the origin of these lineages. Also, we observed common patterns of genome reduction and convergence in metabolic pathway retention. Within a group of Erwinia-associated aphids, horizontal transfer of B-vitamin-biosynthetic genes between endosymbiotic lineages has played an important role in the establishment of the new mutualistic associations. Finally, in the species Cinara strobi, we found that while the species has already acquired a new co-obligate symbiont, it retains the former S. symbiotica symbiont. It keeps a large but highly degenerated genome and has become unable to biosynthetise all B vitamins and essential amino acids, rendering it unable to fulfil its mutualistic role. In brief, the results provided by analysing the genomes of these obligate di- and tri-symbiotic consortia are illuminating the different processes involved in the evolution (from birth to death) of new obligate mutualistic associations betwee

Coming and ceasing to be: Evolution of recent mutualistic associations in aphid endosymbionts

National audienc